Objectif. L’activité physique a des bénéfices sur la santé mentale des personnes vivant avec des troubles psychotiques. L’effort aérobie de type continue étant l’intervention la plus populaire dans la littérature, certaines études ont également étudié le type d’effort de haute intensité par intervalles, mais n’ont pas observé ses effets à long terme. La présente étude vise premièrement à observer le maintien des bénéfices auprès de personnes ayant des troubles psychotiques, après une intervention de six mois de haute intensité par intervalles. Deuxièmement, elle vise à déterminer les prédicteurs de participation à la pratique d’activité physique. Méthodes. Soixante-six sujets (37.9% de femmes, 30.73 ± 7.23 ans) diagnostiqués avec un trouble psychotique selon le DSM-5 ont participé à une intervention supervisée de haute intensité par intervalles de course sur tapis, durant six mois, à raison de deux séances de 30 minutes par semaine. Après cette intervention, il a été offert aux sujets un accès gratuit aux installations ou se sont déroulées les séances pendant à nouveau six mois, sans supervision. Les sujets ont été évalués avant et après l’intervention, puis six mois après l’arrêt de la supervision, soit 12 mois après le premier temps de mesure. La symptomatologie (PANSS), le fonctionnement global (GAF) et social (SOFAS) ont été évalués. Les scores des questionnaires mentionnés ci-dessus ont été analysées statistiquement par des modèles mixtes linéaires et des ANOVA à une voie. Résultats. Les résultats ont montré un maintien de l’impact positif de l’intervention sur les symptômes négatifs (p = 0,004) et globaux (p = 0,01). Les facteurs prédicteurs de la participation aux séances d’activité physique ont montré que les individus ayant participé à moins de 64% des séances sont ceux ayant un moins bon fonctionnement global (GAF : p = 0,02) et social (SOFAS : p ˂ 0,001) et des symptômes plus sévères (PANSS : négatifs : p = 0,02 ; positifs : p = 0,01 ; globaux : p = 0,04). Conclusion. Le maintien des bénéfices n’a été observé qu’au niveau des symptômes négatifs, ce qui implique des stratégies supplémentaires dans l’élaboration de l’intervention et ses modalités. De plus, nos analyses prédictives révèlent qu'une amélioration du fonctionnement social et global, ainsi qu'une réduction de la sévérité des symptômes, sont associées à une participation accrue à l'activité physique chez nos participants. / Aims. Physical activity has mental health benefits for people with psychotic disorders. Continuous aerobic exercise being the most popular intervention in the literature, some studies have also investigated high-intensity interval training but have not investigated its long-term effects. This study had two aims. First, to observe whether the benefits of a six-month high intensity interval training intervention could be maintained among people with psychotic disorders. Second, to determine the predictors of participation in physical activity participation. Methods. Sixty-six subjects (37.9% women, 30.73 ± 7.23 years old) diagnosed with psychotic disorder according to DSM-5 participated in a supervised six-month high-intensity interval treadmill running intervention : twice per week, 30 minutes per session. After the intervention, subjects were offered free access to the facilities where the sessions were held for another six months without supervision. The subjects were evaluated before and after the intervention, and six months after the end of supervision, which was 12 months after the first measurement. Symptomatology (PANSS), global (GAF) and social (SOFAS) functioning were evaluated. The scores of the above-mentioned questionnaires were statistically analyzed using linear mixed models and one-way ANOVA. Results. The results showed a maintenance of the positive impact of the intervention on negative (p = 0.004) and global (p = 0.01) symptoms only. Predictors of participation in physical activity sessions showed that individuals who participated in less than 64% of the sessions had poorer global functioning (GAF: p = 0.02) and social functioning (SOFAS : p ˂ 0,001) and more severe symptoms (PANSS: negative: p = 0.02; positive: p = 0.01; global: p = 0.04). Conclusion. The maintenance of benefits was only observed in terms of negative symptoms, which implies the need for additional strategies in the development and implementation of the intervention. In addition, the prediction analyses of participation in physical activity demonstrated that individuals with better global and social functioning and less severe symptoms are more likely to practice physical activity.

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população geral e estão associados a grande morbidade e disfuncionalidade. Apesar disso, as bases fisiopatológicas destes transtornos ainda estão em investigação. Estudos neuropatológicos post-mortem e de neuroimagem in vivo sugerem haver comprometimento da microestrutura de substância branca (SB) cerebral nestas condições clínicas, associado a alterações da conectividade cerebral. No entanto, nenhuma investigação prévia de neuroimagem avaliou especificamente se tais anormalidades microestruturais podem ser dependentes do estado clínico do paciente, i.e., se tais alterações podem variar de acordo com a fase da doença. Outra linha de investigação biológica em psicoses aponta para alterações na atividade da fosfolipase A2 (PLA2), uma enzima essencial a diversas funções na homeostase cerebral, incluindo manutenção de membrana celular, mielinização e atividade inflamatória. Estudos prévios sugerem haver relação entre alterações na atividade desta enzima e as fases da esquizofrenia. Entretanto, não há estudos translacionais que tenham avaliado como tais alterações se relacionam com anormalidades microestruturais de SB em pacientes psicóticos. OBJETIVOS: Investigar a hipótese de que alterações de microestrutura de SB presentes em pacientes em fase aguda do primeiro episódio psicótico (PEP) sejam potencialmente reversíveis após estabilização clínica; investigar também possíveis alterações estado-dependentes da atividade de PLA2 no PEP; e examinar interações entre manifestações clínicas, microestrutura de SB cerebral e atividade de PLA2 na fisiopatologia do PEP. METODOLOGIA: Pacientes em PEP não afetivo foram avaliados em dois períodos no tempo: durante a fase aguda da doença (T0); após remissão estável de sintomas (T1). Um grupo controle de voluntários saudáveis (CS) também foi avaliado longitudinalmente. Para investigar alterações de microestrutura de SB estado-dependentes, análises voxel-a-voxel de mapas cerebrais de índices de anisotropia (fractional anisotropy, FA) e difusividade (trace, TR) foram conduzidas, assim como o cálculo de correlações entre tais índices de DTI, variáveis clínicas e atividade de PLA2. A atividade dos três principais subgrupos de PLA2 em plaquetas foi estimada através de um método radioenzimático. RESULTADOS: 25 pacientes PEP e 51 CS foram avaliados em T0, com coleta de dados clínico-demográficos, ressonância magnética (RM) e amostra de sangue. Destes, 21 PEP e 36 CS realizaram a segunda aquisição de RM. No baseline (T0), os pacientes PEP apresentaram redução difusa de FA (p < 0,05, FDR), afetando principalmente SB fronto-límbica e fascículos associativos, projetivos e comissurais. As análises longitudinais demonstraram que a remissão clínica se associou a aumentos de FA em tratos de SB acometidos em T0 (p < 0,001, não corrigido), além de robustas correlações inversas entre aumentos de FA e redução sintomas ao longo do tempo (p < 0,05, FDR). As análises de PLA2 não demostraram efeitos estado-dependentes ou correlações consistentes com os índices de DTI. CONCLUSÃO: Alterações da microestrutura de SB afetando tratos cerebrais essenciais para a integração de informação perceptual, cognição e emoções são detectáveis logo após o início do PEP e podem ser parcialmente revertidas em relação direta com a remissão de sintomas psicóticos agudos. Nossos achados reforçam a visão de que anormalidades de SB de tratos cerebrais são um componente neurobiológico central nos transtornos psicóticos agudos, e que a recuperação de tal patologia de SB pode levar à melhora clínica. Por outro lado, a atividade de PLA2 não parece ter associação direta com o estado de doença ou moderar as alterações microestruturais dinâmicas de SB aqui observadas. Estudos com amostras maiores e com um maior número de avaliações ao longo do tempo são necessários para confirmar e ampliar os resultados aqui apresentados / INTRODUCTION: Psychotic disorders are frequent conditions in the general population and are associated to severe morbidity and functional impairment. Notwithstanding, the pathophysiological basis of such disorders is still under investigation. Post-mortem neuropathologic investigations and in vivo neuroimaging studies have pointed to the occurrence of abnormalities in the microstructure of brain white matter (WM) in such clinical conditions, which are associated to changes in brain connectivity. However, no previous neuroimaging investigation has specifically examined whether such microstructural abnormalities would be state-dependent, i.e., whether such changes could relate to the illness phase. Another field of biological investigation in psychosis points to changes in the activity of phospholipase A2 enzyme (PLA2), which is essential to several functions implicated in brain homeostasis, such as the maintenance of cellular membrane, myelination and inflammatory activity. Previous studies suggest the existence of a relationship between changes on PLA2 activity and schizophrenia phase. Nonetheless, no translational study to date has examined the potential interplay between PLA2 activity and WM microstructural abnormalities in psychotic patients. OBJECTIVES: To investigate the hypothesis that WM microstructural changes observed in patients during the acute first-episode psychosis (FEP) are potentially reversible following clinical remission; to investigate possible state-dependent changes in PLA2 activity in FEP; and to examine interactions between clinical manifestations, brain WM microstructure and PLA2 activity in the pathophysiology of FEP. METODOLOGY: Patients with non-affective FEP were evaluated in two time points: during the acute phase (T0) and following sustained remission (T1). A control group of healthy volunteers (HC) was also longitudinally studied. In order to investigate state-dependent WM microstructure changes, voxelwise analyses of brain maps of anisotropy (fractional anisotropy, FA) and diffusivity (trace, TR) indexes were conducted, as well as correlations between such DTI metrics, clinical variables and PLA2 activity. The activity of the three main PLA2 subgroups was assessed in platelets using a radioenzymatic method. RESULTS: 25 FEP and 51 HC were evaluated at T0 (clinical and demographic data, MRI scanning, and blood collection). Out of these, 21 FEP and 36 HC also underwent a second MRI acquisition. At baseline (T0), FEP patients presented widespread reduction of FA (p < 0.05, FDR), affecting mainly fronto-limbic WM and associative, projective and commissural fasciculi. Longitudinal analyses showed that clinical remission was associated with FA increase in WM tracts that were affected at T0 (p < 0.001, uncorrected), besides robust inverse correlations between FA increase and symptoms reduction over time (p < 0.05, FDR). PLA2 analyses failed to show state-dependent effects or consistent correlations to DTI indexes. CONCLUSION: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities are a key neurobiological feature of acute psychotic disorders, and that recovery from such WM pathology can lead to amelioration of symptoms. In the other hand, it seems that PLA2 activity has no direct relationship to the disease state or modulatory effects on the dynamic WM changes observed herein. Studies with larger samples and with more time points evaluations are necessary to confirm and expand the findings reported herein

INTRODUÇÃO: Os transtornos mentais psicóticos são condições frequentes na população geral e estão associados a grande morbidade e disfuncionalidade. Apesar disso, as bases fisiopatológicas destes transtornos ainda estão em investigação. Estudos neuropatológicos post-mortem e de neuroimagem in vivo sugerem haver comprometimento da microestrutura de substância branca (SB) cerebral nestas condições clínicas, associado a alterações da conectividade cerebral. No entanto, nenhuma investigação prévia de neuroimagem avaliou especificamente se tais anormalidades microestruturais podem ser dependentes do estado clínico do paciente, i.e., se tais alterações podem variar de acordo com a fase da doença. Outra linha de investigação biológica em psicoses aponta para alterações na atividade da fosfolipase A2 (PLA2), uma enzima essencial a diversas funções na homeostase cerebral, incluindo manutenção de membrana celular, mielinização e atividade inflamatória. Estudos prévios sugerem haver relação entre alterações na atividade desta enzima e as fases da esquizofrenia. Entretanto, não há estudos translacionais que tenham avaliado como tais alterações se relacionam com anormalidades microestruturais de SB em pacientes psicóticos. OBJETIVOS: Investigar a hipótese de que alterações de microestrutura de SB presentes em pacientes em fase aguda do primeiro episódio psicótico (PEP) sejam potencialmente reversíveis após estabilização clínica; investigar também possíveis alterações estado-dependentes da atividade de PLA2 no PEP; e examinar interações entre manifestações clínicas, microestrutura de SB cerebral e atividade de PLA2 na fisiopatologia do PEP. METODOLOGIA: Pacientes em PEP não afetivo foram avaliados em dois períodos no tempo: durante a fase aguda da doença (T0); após remissão estável de sintomas (T1). Um grupo controle de voluntários saudáveis (CS) também foi avaliado longitudinalmente. Para investigar alterações de microestrutura de SB estado-dependentes, análises voxel-a-voxel de mapas cerebrais de índices de anisotropia (fractional anisotropy, FA) e difusividade (trace, TR) foram conduzidas, assim como o cálculo de correlações entre tais índices de DTI, variáveis clínicas e atividade de PLA2. A atividade dos três principais subgrupos de PLA2 em plaquetas foi estimada através de um método radioenzimático. RESULTADOS: 25 pacientes PEP e 51 CS foram avaliados em T0, com coleta de dados clínico-demográficos, ressonância magnética (RM) e amostra de sangue. Destes, 21 PEP e 36 CS realizaram a segunda aquisição de RM. No baseline (T0), os pacientes PEP apresentaram redução difusa de FA (p < 0,05, FDR), afetando principalmente SB fronto-límbica e fascículos associativos, projetivos e comissurais. As análises longitudinais demonstraram que a remissão clínica se associou a aumentos de FA em tratos de SB acometidos em T0 (p < 0,001, não corrigido), além de robustas correlações inversas entre aumentos de FA e redução sintomas ao longo do tempo (p < 0,05, FDR). As análises de PLA2 não demostraram efeitos estado-dependentes ou correlações consistentes com os índices de DTI. CONCLUSÃO: Alterações da microestrutura de SB afetando tratos cerebrais essenciais para a integração de informação perceptual, cognição e emoções são detectáveis logo após o início do PEP e podem ser parcialmente revertidas em relação direta com a remissão de sintomas psicóticos agudos. Nossos achados reforçam a visão de que anormalidades de SB de tratos cerebrais são um componente neurobiológico central nos transtornos psicóticos agudos, e que a recuperação de tal patologia de SB pode levar à melhora clínica. Por outro lado, a atividade de PLA2 não parece ter associação direta com o estado de doença ou moderar as alterações microestruturais dinâmicas de SB aqui observadas. Estudos com amostras maiores e com um maior número de avaliações ao longo do tempo são necessários para confirmar e ampliar os resultados aqui apresentados / INTRODUCTION: Psychotic disorders are frequent conditions in the general population and are associated to severe morbidity and functional impairment. Notwithstanding, the pathophysiological basis of such disorders is still under investigation. Post-mortem neuropathologic investigations and in vivo neuroimaging studies have pointed to the occurrence of abnormalities in the microstructure of brain white matter (WM) in such clinical conditions, which are associated to changes in brain connectivity. However, no previous neuroimaging investigation has specifically examined whether such microstructural abnormalities would be state-dependent, i.e., whether such changes could relate to the illness phase. Another field of biological investigation in psychosis points to changes in the activity of phospholipase A2 enzyme (PLA2), which is essential to several functions implicated in brain homeostasis, such as the maintenance of cellular membrane, myelination and inflammatory activity. Previous studies suggest the existence of a relationship between changes on PLA2 activity and schizophrenia phase. Nonetheless, no translational study to date has examined the potential interplay between PLA2 activity and WM microstructural abnormalities in psychotic patients. OBJECTIVES: To investigate the hypothesis that WM microstructural changes observed in patients during the acute first-episode psychosis (FEP) are potentially reversible following clinical remission; to investigate possible state-dependent changes in PLA2 activity in FEP; and to examine interactions between clinical manifestations, brain WM microstructure and PLA2 activity in the pathophysiology of FEP. METODOLOGY: Patients with non-affective FEP were evaluated in two time points: during the acute phase (T0) and following sustained remission (T1). A control group of healthy volunteers (HC) was also longitudinally studied. In order to investigate state-dependent WM microstructure changes, voxelwise analyses of brain maps of anisotropy (fractional anisotropy, FA) and diffusivity (trace, TR) indexes were conducted, as well as correlations between such DTI metrics, clinical variables and PLA2 activity. The activity of the three main PLA2 subgroups was assessed in platelets using a radioenzymatic method. RESULTS: 25 FEP and 51 HC were evaluated at T0 (clinical and demographic data, MRI scanning, and blood collection). Out of these, 21 FEP and 36 HC also underwent a second MRI acquisition. At baseline (T0), FEP patients presented widespread reduction of FA (p < 0.05, FDR), affecting mainly fronto-limbic WM and associative, projective and commissural fasciculi. Longitudinal analyses showed that clinical remission was associated with FA increase in WM tracts that were affected at T0 (p < 0.001, uncorrected), besides robust inverse correlations between FA increase and symptoms reduction over time (p < 0.05, FDR). PLA2 analyses failed to show state-dependent effects or consistent correlations to DTI indexes. CONCLUSION: WM changes affecting brain tracts critical to the integration of perceptual information, cognition and emotions are detectable soon after the onset of FEP and may partially reverse in direct relation to the remission of acute psychotic symptoms. Our findings reinforce the view that WM abnormalities are a key neurobiological feature of acute psychotic disorders, and that recovery from such WM pathology can lead to amelioration of symptoms. In the other hand, it seems that PLA2 activity has no direct relationship to the disease state or modulatory effects on the dynamic WM changes observed herein. Studies with larger samples and with more time points evaluations are necessary to confirm and expand the findings reported herein

Au cours des dernières décennies, de nombreuses études ont confirmé l’existence d’une relation entre les troubles mentaux graves et persistants (TMGP) et la commission de crimes violents. Les facteurs de risque associés à la violence chez les gens atteints de TMGP sont la consommation d’alcool ou de drogues, la dépression et les troubles de personnalité. Cependant, aucune étude n’a été faite auprès des détenus des prisons québécoises, c’est-à-dire, des détenus qui purgent des sentences de courte durée, afin de voir si ces constats s’appliquent aussi à cette population. La présente étude tente de vérifier si les mêmes facteurs de risque sont liés à la violence chez les détenus psychotiques des prisons du Québec. Les dossiers de la RAMQ et du système DACOR de 121 détenus ont été analysés afin de répondre à la question de recherche. Tout d’abord, des analyses statistiques descriptives et bivariées ont été effectuées. Par la suite, des régressions logistiques ont été menées afin d’identifier les meilleurs prédicteurs de comportements violents chez les contrevenants psychotiques des prisons québécoises. Il semble que ce soit davantage les antécédents judiciaires ainsi que la médication psychotrope qui a été prescrite, plutôt que les diagnostics de troubles mentaux comorbides, qui distinguent les détenus psychotiques violents des non-violents dans les prisons québécoises. Une explication possible à cette observation est que les médecins prescriraient plus en fonction de la présence de certains symptômes spécifiques qu’en fonction des diagnostics de l’axe I ou de l’axe II. Enfin, des différences significatives sont présentes entre les hommes et les femmes. / During the past decades, many studies have confirmed the existence of a relationship between severe and persistent mental disorders (SPMD) and the commission of violent crimes. Risk factors associated with violence in mentally disordered violent offenders are: alcohol and drug consumption, depression and personality disorders. However, no study has been conducted among inmates serving short sentences in Québec’s jails, to see if these findings apply to them. Our study attempts to verify whether the same risk factors are associated with violence among psychotic inmates of Quebec’s correctional facilities. The RAMQ and DACOR files of 121 incarcerated offenders were analyzed to answer the research question. To begin, descriptive and bi-variate analyses were conducted. Then, logistic regressions were carried out to identify the best predictors of violent behaviours among Québec’s psychotic offenders. It seems that it is criminal antecedents and psychotropic drugs rather than comorbid mental disorders that distinguish the violent from the non-violent psychotic offenders in Québec’s jails. A possible explanation for this observation is that physicians prescribe drugs in function of the presence of specific symptoms rather than in function of axis I or axis II diagnosis. Moreover, significant differences were found between men and women.

L’existence d’un sous-type dissociatif de schizophrénie a été suggérée par plusieurs auteurs pour rendre compte des présentations symptomatologiques d’un groupe de personnes dont le diagnostic principal est dans le spectre de la schizophrénie mais qui présentent aussi des symptômes dissociatifs (Ross, 2004; Şar et al., 2010; Van der Hart, Witztum, & Friedman, 1993). D’origine traumatique, ce type de portrait clinique où symptômes psychotiques et dissociatifs s’entremêlent aurait été décrit il y a déjà plus d’un siècle (Janet & Raymond, 1898) mais serait disparu dans les années ’30, assimilé au concept de « schizophrénie » (Rosenbaum, 1980). C’est dans un nouveau contexte nosographique que le concept de schizophrénie dissociative refait surface. En effet, la nosographie psychiatrique a pris un tournant en 1980 lorsque l’approche préconisée par le DSM est devenue descriptive plutôt que basée sur des conceptualisations psychanalytiques. Du coup, les affections d’alors ont été divisées en troubles dont les symptômes ont tendance à se manifester ensemble (Cooper, 2004) et la comorbidité entre les troubles a augmenté. Étant donné la comorbidité fréquemment rapportée entre les troubles psychotiques et dissociatifs, la similarité phénoménologique de leurs symptômes, ainsi que leur possible étiologie traumatique, Ross (2004) a proposé une série de critères permettant de diagnostiquer une schizophrénie dissociative. L’objectif principal de cette thèse est donc d’établir si la schizophrénie dissociative, telle que définie par Ross (2004), existe. Le premier article porte sur la problématique et le contexte théorique ayant mené à la question de recherche. Il vise à faire un survol des enjeux entourant la question de la schizophrénie dissociative et rend compte des écrits scientifiques sur la symptomatologie similaire entre les troubles psychotiques et dissociatifs, sur leur étiologie traumatique et sur les études sur la dissociation et la schizophrénie. Le deuxième article est quant à lui un article empirique rendant compte de la méthodologie utilisée pour répondre à la question de recherche. En effet, aucune étude jusqu’ici n’a testé systématiquement les critères de la schizophrénie dissociative. Nos résultats démontrent que 24% de notre échantillon (N=50) pourrait recevoir le diagnostic de schizophrénie dissociative avec les critères proposés par Ross (2004). Toutefois, ces critères posant problème, une modification a été proposée et une prévalence de 14% a alors été trouvée. Des vignettes cliniques sont présentées afin de comparer nos participants avec ceux rapportés ailleurs. Les liens entre symptômes psychotiques et dissociatifs sont discutés en essayant de conceptualiser la schizophrénie dissociative de différentes manières, soit comme une nouvelle entité clinique, comme un trouble comorbide ou dans un contexte nosographique psychodynamique. / The existence of a dissociative subtype of schizophrenia has been suggested by several authors to account for the symptomatology of a group of people whose primary diagnosis is in the schizophrenia spectrum but have in addition dissociative symptoms (Ross, 2004; Sar et al, 2010; Van der Hart, Witztum, & Friedman, 1993). Of traumatic origin, this type of clinical picture where psychotic and dissociative symptoms are intertwined was first described more than a century ago (Janet & Raymond, 1898) but disappeared in the 30’s, having been incorporated to the concept of "schizophrenia" (Rosenbaum, 1980). It is in a new nosographic context that the concept of dissociative schizophrenia resurfaced. Indeed, psychiatric nosography took a turn in 1980 when the approach advocated by the DSM became descriptive rather than based on psychoanalytic conceptualizations. The psychiatric conditions of the time were divided into disorders whose symptoms tended to occur together (Cooper, 2004). Consequently, the presence of comorbid disorders increased. Given the frequently reported co-occurrence of psychotic and dissociative disorders, the phenomenological similarity of their symptoms and their potential traumatic etiology, Ross (2004) proposed a criteria set for the diagnosis of dissociative schizophrenia. The main objective of this thesis is to determine whether the dissociative schizophrenia, as defined by Ross (2004), exists. The first article focuses on the problem and the theoretical background that led to the research question. It aims at providing an overview of the issues surrounding the question of dissociative schizophrenia. It also reports on the literature pertaining to symptoms found in both psychotic and dissociative disorders, their traumatic etiology and studies on dissociation and schizophrenia. The second article is of empirical nature and reports the methodology used to answer the research question. Indeed, no study to date has systematically tested the criteria for dissociative schizophrenia. Our results show that 24 % of our sample (N = 50) could receive a diagnosis of schizophrenia with dissociative criteria proposed by Ross (2004). However, the criteria set was problematic so a modification was proposed and a prevalence of 14% was then found. Clinical vignettes are presented to compare our participants with those reported elsewhere. The links between psychotic and dissociative symptoms are discussed in trying to conceptualize dissociative schizophrenia in different ways, either as a new clinical entity, as a comorbid disorder or in a psychodynamic nosographic context.

A epilepsia é um transtorno do funcionamento cerebral caracterizado por crises epilépticas recorrentes que acomete cerca de 1 a 2% da população mundial. A epilepsia do lobo temporal (ELT) é o subtipo mais prevalente. A refratariedade aos medicamentos é comum e cerca de 40 % destes pacientes apresentam transtornos psiquiátricos. Neste trabalho utilizamos o método de TacMan real time PCR para quantificar o mRNA de subtipos dos receptores de noradrenalina, dopamina, serotonina e substância P em hipocampos cirurgicamente removidos de pacientes com ELT para conhecer o papel destes na ELT com ou sem comorbidade psiquiátrica (depressão ou psicose). Nossa amostra foi de 48 pacientes com ELT sem (Epilepsia - 24) ou com comorbidade psicótica (Psicose - 10) ou depressiva (Depressão - 14) e 8 Controles (necrópsias). O receptor adrenérgico-&#945;2A (AD2A) apresentou diferença entre os grupos (p = 0,0059) com significância para a variável Antiepiléptico (p = 0,0374) e pós-teste significante de maior expressão do mRNA de AD2A no grupo Epilepsia comparado com Controle e com Psicose. A ativação dos receptores &#945;2A no hipocampo pelos antiepilépticos pode explicar nossos achados do grupo Epilepsia comparado ao Controle, corroborando a literatura acerca do AD2A na epilepsia e em relação aos antiepilépticos. O AD2C mostrou diferença entre os grupos (p = 0,0016), sem significância nas variáveis de controle e significante maior expressão do mRNA de AD2C no grupo Epilepsia comparado ao Controle e Psicose. O AD2C é encontrado em áreas que processam informações sensoriais e controlam atividades motoras e emocionais relacionadas, o que pode explicar nossos resultados. Parece ser importante na patologia relacionada à ELT e merece ser estudado. A não diferença entre Epilepsia e Depressão para AD2A e AD2C, parecem confirmar uma relação bi-direcional ou um mecanismo patogênico comum entre epilepsia e depressão, enquanto a menor expressão de AD2A e AD2C nos psicóticos parece indicar diferenças nos mecanismos adrenérgicos ligados a psicose e epilepsia. D2 mostrou diferença entre os grupos (p = 0,0125) com resultado significativo para a variável Subtipo de Diagnóstico Psiquiátrico (p = 0,0239), provavelmente devido a cronicidade da doença e a quantidade de episódios depressivos apresentados pelos sujeitos. Quanto maior a freqüência das crises (p = 0,0381) maior a expressão do D2 no grupo Epilepsia e no Depressão comparados ao Controle. Estes achados sugerem a participação deste receptor na depressão comórbida na ELT; corroboram que o monitoramento dopaminérgico límbico pode ser útil para desenvolver novos antidepressivos e propõem pesquisas futuras sobre D2 em epilépticos. A participação de 5-HT2A na ELT é indicada, pois, sua maior expressão no grupo Epilepsia em relação ao Controle foi significativa (p = 0,0273). Quanto maior a freqüência das crises epilépticas maior a expressão do 5-HT2A (p = 0, 0433). Não encontramos resultados significativos referentes aos receptores D4, 5-HT1A, 5-HT2C e NK1. Nossos resultados mostraram a possibilidade da aplicação do TacMan real time PCR no estudo de receptores de neurotransmissores, sugeriu a importância dos receptores estudados na ELT e comorbidades psiquiátricas, e que outras estruturas límbicas, como a amígdala, sejam focos de investigação. / Epilepsy is a mental functional disorder characterized by recurrent seizures that affect about 1 to 2% of world population. Temporal lobe epilepsy (TLE) is the most prevalent subtype. The refractory to medication is common and about 40% of these patients have psychiatric disorders. This study used the TacMan real time PCR method to quantify noradrenergic, dopaminergic, serotoninergic and substance P receptors subtypes mRNA expression in hippocampus surgically removed from patients with TLE to know their role in TLE with or without psychiatric commorbity (depression or psychosis). Our sample consisted of 48 TLE patients without (Epilepsy - 24) or with psychotic (Psychosis - 10) or depressive (Depression - 14) commorbity and 8 Controls (necropsies). The &#945;2A adrenergic receptor (AD2A) showed difference between groups (p = 0.0059) with significance for Antiepileptic Medication variable (p = 0.0374) and post-hoc test significantly greater AD2A mRNA expression of Epilepsy group compared with Control and Psychosis. The activation of hippocampus &#945;2A receptors by antiepileptic drugs can explain our findings of the Epilepsy group compared with Control, corroborating the literature about the AD2A in epilepsy and for antiepileptic drugs. The AD2C showed differences between groups (p = 0.0016) without significance in the variables of control and significantly greater AD2C mRNA expression of the Epilepsy group compared to Control and Psychosis. The AD2C is found in areas that process sensory information and control motor and emotional related activities, which may explain our results. It seems to be important in the pathology related to TLE and deserves to be studied. No differences between Epilepsy and Depression to AD2A and AD2C seem to confirm a bi-directional relation or a common pathogenic mechanism between epilepsy and depression, while the lowest AD2A and AD2C expression within psychotics seem suggests differences in adrenergic mechanisms linked to psychosis and epilepsy. D2 showed differences between groups (p = 0.0125) with significant results for the variable Subtype of Psychiatric Diagnosis (p = 0.0239), probably due to chronic disease and the number of depressive episodes presented by subjects. The higher the frequency of seizures (p = 0.0381) the higher was the D2 expression within Epilepsy group compared with Control and Depression compared to Control. These findings suggest the involvement of this receptor in TLE commorbid depression; corroborate that limbic dopaminergic monitoring may be useful in developing new antidepressants and propose future research on D2 in epileptics. The participation of 5-HT2A in TLE is indicated, therefore its significant higher expression in the Epilepsy group in relation to Control (p = 0.0273). The higher the frequency of seizures the higher was the 5-HT2A expression (p = 0.0433). We found no significant results for the D4, 5-HT1A, 5-HT2C and NK1 receptors. Our results showed the possibility of TacMan real time PCR method application in TLE neurotransmission receptors study, suggested the importance of the studied receptors in TLE and psychiatric commorbities and that other limbic structures, as the amygdala, should be investigation targets.

Os transtornos afetivos são altamente prevalentes dentre os transtornos mentais, principalmente Transtorno Afetivo Bipolar (TAB) e Depressão Maior Unipolar (DMU), apresentando altas taxas de morbi-mortalidade. Estudos prévios de Ressonância Magnética (RM) têm identificado anormalidades estruturais cerebrais em indivíduos com TAB e DMU quando comparados a controles normais. Entretanto, nenhum destes estudos foi realizado a partir da comparação direta entre pacientes com DMU e TAB de início recente, nem comparou separadamente tais grupos com amostras representativas de controles assintomáticos provenientes de mesma região geográfica. No presente estudo, definimos a priori que regiões do circuito córtico-límbico-talâmico-estriatal estariam alteradas quando comparados indivíduos com TAB, DMU e controles normais diretamente entre si, em amostra de pacientes com quadros graves de sintomatologia psicótica e pareada com controles normais selecionados na mesma área geográfica dos pacientes. Foram selecionados 46 pacientes (20 com DMU e 26 com TAB) que tiveram contato pela primeira vez com serviço de saúde mental após início de sintomas psicóticos e 62 controles normais. Tanto pacientes quanto controles foram submetidos à RM em aparelho de 1,5 Tesla. Os diagnósticos foram baseados no DSM-IV e confirmados após 1 ano da realização da RM. As imagens foram analisadas pelo método automatizado de processamento denominado morfometria baseada no voxel (voxel-based morphometry). A comparação entre os grupos mostrou redução significativa de substância cinzenta regional em pacientes com DMU comparados aos controles (p<0,05, corrigido para comparações múltiplas) em duas regiões cerebrais selecionadas a priori: córtex pré-frontal dorsolateral (CPFDL) bilateralmente e giro parahipocampal posterior esquerdo. Na comparação direta entre pacientes com DMU e TAB encontramos uma redução de substância cinzenta de CPFDL direito em pacientes com DMU, como tendência a significância estatística (p<0,10, corrigido para comparações múltiplas). Nossos achados mostram que anormalidades volumétricas de CPFDL e região temporal medial estão presentes em pacientes com DMU em primeiro episódio psicótico, mas não em pacientes com TAB com gravidade de sintomas semelhante. / Affective disorders are highly prevalent mental disorders, mainly Major Depressive Disorder (MDD) and Bipolar Disorder (BD), with high morbidity and mortality rates. Previous morphometric magnetic resonance imaging (MRI) studies have identified brain volumetric abnormalities in samples of subjects suffering from MDD or BD. However, none of these have conducted direct brain volume comparisons between patients with recent-onset MDD and BD, nor contrasted them separately against representative groups of asymptomatic controls recruited from exactly the same environment. In the present study, we defined a priori that brain regions involved in cortico-limbic-thalamic-striatal circuits would present volume abnormalities when comparing subjects with MDD and BD with psychotic features, in their first contact with the health care system in Brazil, and a control sample of next-door asymptomatic neighbors. Forty-six patients (20 MDD and 26 BD) and 62 controls were examined with MRI, using an equipment of 1.5 Tesla. Diagnoses were based on DSM-IV, and confirmed one year after scanning. Image processing was conducted using voxel-based morphometry methods. Between-group comparisons showed significant regional gray matter deficits in MDD subjects relative to controls (p<0.05, corrected for multiple comparisons), involving two brain regions where abnormalities in mood disorder patients had been predicted a priori: the dorsolateral prefrontal cortex (DLPFC) bilaterally and the left posterior parahippocampal gyrus. In the direct comparison between MDD and BD patients, the right-sided finding of decreased DLPFC gray matter in the former group retained trend levels of significance (p<0.10 corrected). Our findings indicate that significant structural abnormalities of the DLPFC and medial temporal region are present in patients with MDD in their first episode with psychotic features, but not in BD subjects with symptoms of similar severity.

A epilepsia é um transtorno do funcionamento cerebral caracterizado por crises epilépticas recorrentes que acomete cerca de 1 a 2% da população mundial. A epilepsia do lobo temporal (ELT) é o subtipo mais prevalente. A refratariedade aos medicamentos é comum e cerca de 40 % destes pacientes apresentam transtornos psiquiátricos. Neste trabalho utilizamos o método de TacMan real time PCR para quantificar o mRNA de subtipos dos receptores de noradrenalina, dopamina, serotonina e substância P em hipocampos cirurgicamente removidos de pacientes com ELT para conhecer o papel destes na ELT com ou sem comorbidade psiquiátrica (depressão ou psicose). Nossa amostra foi de 48 pacientes com ELT sem (Epilepsia - 24) ou com comorbidade psicótica (Psicose - 10) ou depressiva (Depressão - 14) e 8 Controles (necrópsias). O receptor adrenérgico-&#945;2A (AD2A) apresentou diferença entre os grupos (p = 0,0059) com significância para a variável Antiepiléptico (p = 0,0374) e pós-teste significante de maior expressão do mRNA de AD2A no grupo Epilepsia comparado com Controle e com Psicose. A ativação dos receptores &#945;2A no hipocampo pelos antiepilépticos pode explicar nossos achados do grupo Epilepsia comparado ao Controle, corroborando a literatura acerca do AD2A na epilepsia e em relação aos antiepilépticos. O AD2C mostrou diferença entre os grupos (p = 0,0016), sem significância nas variáveis de controle e significante maior expressão do mRNA de AD2C no grupo Epilepsia comparado ao Controle e Psicose. O AD2C é encontrado em áreas que processam informações sensoriais e controlam atividades motoras e emocionais relacionadas, o que pode explicar nossos resultados. Parece ser importante na patologia relacionada à ELT e merece ser estudado. A não diferença entre Epilepsia e Depressão para AD2A e AD2C, parecem confirmar uma relação bi-direcional ou um mecanismo patogênico comum entre epilepsia e depressão, enquanto a menor expressão de AD2A e AD2C nos psicóticos parece indicar diferenças nos mecanismos adrenérgicos ligados a psicose e epilepsia. D2 mostrou diferença entre os grupos (p = 0,0125) com resultado significativo para a variável Subtipo de Diagnóstico Psiquiátrico (p = 0,0239), provavelmente devido a cronicidade da doença e a quantidade de episódios depressivos apresentados pelos sujeitos. Quanto maior a freqüência das crises (p = 0,0381) maior a expressão do D2 no grupo Epilepsia e no Depressão comparados ao Controle. Estes achados sugerem a participação deste receptor na depressão comórbida na ELT; corroboram que o monitoramento dopaminérgico límbico pode ser útil para desenvolver novos antidepressivos e propõem pesquisas futuras sobre D2 em epilépticos. A participação de 5-HT2A na ELT é indicada, pois, sua maior expressão no grupo Epilepsia em relação ao Controle foi significativa (p = 0,0273). Quanto maior a freqüência das crises epilépticas maior a expressão do 5-HT2A (p = 0, 0433). Não encontramos resultados significativos referentes aos receptores D4, 5-HT1A, 5-HT2C e NK1. Nossos resultados mostraram a possibilidade da aplicação do TacMan real time PCR no estudo de receptores de neurotransmissores, sugeriu a importância dos receptores estudados na ELT e comorbidades psiquiátricas, e que outras estruturas límbicas, como a amígdala, sejam focos de investigação. / Epilepsy is a mental functional disorder characterized by recurrent seizures that affect about 1 to 2% of world population. Temporal lobe epilepsy (TLE) is the most prevalent subtype. The refractory to medication is common and about 40% of these patients have psychiatric disorders. This study used the TacMan real time PCR method to quantify noradrenergic, dopaminergic, serotoninergic and substance P receptors subtypes mRNA expression in hippocampus surgically removed from patients with TLE to know their role in TLE with or without psychiatric commorbity (depression or psychosis). Our sample consisted of 48 TLE patients without (Epilepsy - 24) or with psychotic (Psychosis - 10) or depressive (Depression - 14) commorbity and 8 Controls (necropsies). The &#945;2A adrenergic receptor (AD2A) showed difference between groups (p = 0.0059) with significance for Antiepileptic Medication variable (p = 0.0374) and post-hoc test significantly greater AD2A mRNA expression of Epilepsy group compared with Control and Psychosis. The activation of hippocampus &#945;2A receptors by antiepileptic drugs can explain our findings of the Epilepsy group compared with Control, corroborating the literature about the AD2A in epilepsy and for antiepileptic drugs. The AD2C showed differences between groups (p = 0.0016) without significance in the variables of control and significantly greater AD2C mRNA expression of the Epilepsy group compared to Control and Psychosis. The AD2C is found in areas that process sensory information and control motor and emotional related activities, which may explain our results. It seems to be important in the pathology related to TLE and deserves to be studied. No differences between Epilepsy and Depression to AD2A and AD2C seem to confirm a bi-directional relation or a common pathogenic mechanism between epilepsy and depression, while the lowest AD2A and AD2C expression within psychotics seem suggests differences in adrenergic mechanisms linked to psychosis and epilepsy. D2 showed differences between groups (p = 0.0125) with significant results for the variable Subtype of Psychiatric Diagnosis (p = 0.0239), probably due to chronic disease and the number of depressive episodes presented by subjects. The higher the frequency of seizures (p = 0.0381) the higher was the D2 expression within Epilepsy group compared with Control and Depression compared to Control. These findings suggest the involvement of this receptor in TLE commorbid depression; corroborate that limbic dopaminergic monitoring may be useful in developing new antidepressants and propose future research on D2 in epileptics. The participation of 5-HT2A in TLE is indicated, therefore its significant higher expression in the Epilepsy group in relation to Control (p = 0.0273). The higher the frequency of seizures the higher was the 5-HT2A expression (p = 0.0433). We found no significant results for the D4, 5-HT1A, 5-HT2C and NK1 receptors. Our results showed the possibility of TacMan real time PCR method application in TLE neurotransmission receptors study, suggested the importance of the studied receptors in TLE and psychiatric commorbities and that other limbic structures, as the amygdala, should be investigation targets.

Au cours des dernières décennies, de nombreuses études ont confirmé l’existence d’une relation entre les troubles mentaux graves et persistants (TMGP) et la commission de crimes violents. Les facteurs de risque associés à la violence chez les gens atteints de TMGP sont la consommation d’alcool ou de drogues, la dépression et les troubles de personnalité. Cependant, aucune étude n’a été faite auprès des détenus des prisons québécoises, c’est-à-dire, des détenus qui purgent des sentences de courte durée, afin de voir si ces constats s’appliquent aussi à cette population. La présente étude tente de vérifier si les mêmes facteurs de risque sont liés à la violence chez les détenus psychotiques des prisons du Québec. Les dossiers de la RAMQ et du système DACOR de 121 détenus ont été analysés afin de répondre à la question de recherche. Tout d’abord, des analyses statistiques descriptives et bivariées ont été effectuées. Par la suite, des régressions logistiques ont été menées afin d’identifier les meilleurs prédicteurs de comportements violents chez les contrevenants psychotiques des prisons québécoises. Il semble que ce soit davantage les antécédents judiciaires ainsi que la médication psychotrope qui a été prescrite, plutôt que les diagnostics de troubles mentaux comorbides, qui distinguent les détenus psychotiques violents des non-violents dans les prisons québécoises. Une explication possible à cette observation est que les médecins prescriraient plus en fonction de la présence de certains symptômes spécifiques qu’en fonction des diagnostics de l’axe I ou de l’axe II. Enfin, des différences significatives sont présentes entre les hommes et les femmes. / During the past decades, many studies have confirmed the existence of a relationship between severe and persistent mental disorders (SPMD) and the commission of violent crimes. Risk factors associated with violence in mentally disordered violent offenders are: alcohol and drug consumption, depression and personality disorders. However, no study has been conducted among inmates serving short sentences in Québec’s jails, to see if these findings apply to them. Our study attempts to verify whether the same risk factors are associated with violence among psychotic inmates of Quebec’s correctional facilities. The RAMQ and DACOR files of 121 incarcerated offenders were analyzed to answer the research question. To begin, descriptive and bi-variate analyses were conducted. Then, logistic regressions were carried out to identify the best predictors of violent behaviours among Québec’s psychotic offenders. It seems that it is criminal antecedents and psychotropic drugs rather than comorbid mental disorders that distinguish the violent from the non-violent psychotic offenders in Québec’s jails. A possible explanation for this observation is that physicians prescribe drugs in function of the presence of specific symptoms rather than in function of axis I or axis II diagnosis. Moreover, significant differences were found between men and women.

L’existence d’un sous-type dissociatif de schizophrénie a été suggérée par plusieurs auteurs pour rendre compte des présentations symptomatologiques d’un groupe de personnes dont le diagnostic principal est dans le spectre de la schizophrénie mais qui présentent aussi des symptômes dissociatifs (Ross, 2004; Şar et al., 2010; Van der Hart, Witztum, & Friedman, 1993). D’origine traumatique, ce type de portrait clinique où symptômes psychotiques et dissociatifs s’entremêlent aurait été décrit il y a déjà plus d’un siècle (Janet & Raymond, 1898) mais serait disparu dans les années ’30, assimilé au concept de « schizophrénie » (Rosenbaum, 1980). C’est dans un nouveau contexte nosographique que le concept de schizophrénie dissociative refait surface. En effet, la nosographie psychiatrique a pris un tournant en 1980 lorsque l’approche préconisée par le DSM est devenue descriptive plutôt que basée sur des conceptualisations psychanalytiques. Du coup, les affections d’alors ont été divisées en troubles dont les symptômes ont tendance à se manifester ensemble (Cooper, 2004) et la comorbidité entre les troubles a augmenté. Étant donné la comorbidité fréquemment rapportée entre les troubles psychotiques et dissociatifs, la similarité phénoménologique de leurs symptômes, ainsi que leur possible étiologie traumatique, Ross (2004) a proposé une série de critères permettant de diagnostiquer une schizophrénie dissociative. L’objectif principal de cette thèse est donc d’établir si la schizophrénie dissociative, telle que définie par Ross (2004), existe. Le premier article porte sur la problématique et le contexte théorique ayant mené à la question de recherche. Il vise à faire un survol des enjeux entourant la question de la schizophrénie dissociative et rend compte des écrits scientifiques sur la symptomatologie similaire entre les troubles psychotiques et dissociatifs, sur leur étiologie traumatique et sur les études sur la dissociation et la schizophrénie. Le deuxième article est quant à lui un article empirique rendant compte de la méthodologie utilisée pour répondre à la question de recherche. En effet, aucune étude jusqu’ici n’a testé systématiquement les critères de la schizophrénie dissociative. Nos résultats démontrent que 24% de notre échantillon (N=50) pourrait recevoir le diagnostic de schizophrénie dissociative avec les critères proposés par Ross (2004). Toutefois, ces critères posant problème, une modification a été proposée et une prévalence de 14% a alors été trouvée. Des vignettes cliniques sont présentées afin de comparer nos participants avec ceux rapportés ailleurs. Les liens entre symptômes psychotiques et dissociatifs sont discutés en essayant de conceptualiser la schizophrénie dissociative de différentes manières, soit comme une nouvelle entité clinique, comme un trouble comorbide ou dans un contexte nosographique psychodynamique. / The existence of a dissociative subtype of schizophrenia has been suggested by several authors to account for the symptomatology of a group of people whose primary diagnosis is in the schizophrenia spectrum but have in addition dissociative symptoms (Ross, 2004; Sar et al, 2010; Van der Hart, Witztum, & Friedman, 1993). Of traumatic origin, this type of clinical picture where psychotic and dissociative symptoms are intertwined was first described more than a century ago (Janet & Raymond, 1898) but disappeared in the 30’s, having been incorporated to the concept of "schizophrenia" (Rosenbaum, 1980). It is in a new nosographic context that the concept of dissociative schizophrenia resurfaced. Indeed, psychiatric nosography took a turn in 1980 when the approach advocated by the DSM became descriptive rather than based on psychoanalytic conceptualizations. The psychiatric conditions of the time were divided into disorders whose symptoms tended to occur together (Cooper, 2004). Consequently, the presence of comorbid disorders increased. Given the frequently reported co-occurrence of psychotic and dissociative disorders, the phenomenological similarity of their symptoms and their potential traumatic etiology, Ross (2004) proposed a criteria set for the diagnosis of dissociative schizophrenia. The main objective of this thesis is to determine whether the dissociative schizophrenia, as defined by Ross (2004), exists. The first article focuses on the problem and the theoretical background that led to the research question. It aims at providing an overview of the issues surrounding the question of dissociative schizophrenia. It also reports on the literature pertaining to symptoms found in both psychotic and dissociative disorders, their traumatic etiology and studies on dissociation and schizophrenia. The second article is of empirical nature and reports the methodology used to answer the research question. Indeed, no study to date has systematically tested the criteria for dissociative schizophrenia. Our results show that 24 % of our sample (N = 50) could receive a diagnosis of schizophrenia with dissociative criteria proposed by Ross (2004). However, the criteria set was problematic so a modification was proposed and a prevalence of 14% was then found. Clinical vignettes are presented to compare our participants with those reported elsewhere. The links between psychotic and dissociative symptoms are discussed in trying to conceptualize dissociative schizophrenia in different ways, either as a new clinical entity, as a comorbid disorder or in a psychodynamic nosographic context.